LIMITS OF HUMAN

TOLERANCE TO HYPOXIA

Paolo Cerretelli
Dipartimento di Scienze e Tecnologie
Biomediche Universit di MIlano

Arica, April 2005

1. AEROBIC METABOLISM
Barometric Pressure as a function of altitude

800

700 PB

600

500 Eq. Zuntz

PB (Torr)

400 Mt. Everest

PB=253 Torr
ICAO

300

200 PAO2 (Torr)

50
PAO2
37.6
0
0 2 4 6 8 10

Altitude (km)
Alveolar and arterial blood gas pressures at
the summit of Mt. Everest (8850m)

Arterial

Barometri Alveolar
Altitude c pressure Inspired PO2
(m) PO2 PO2 PCO2 pH SaO2
(torr) (torr)
(torr)

8848 253 43 35 28 7.5 > 7.7 70

Sea
760 149 100 95 40 7.4 97
Level
Predicted ceiling for climbs without supplementary
oxygen based on estimated alveolar gas values
(Margaria, 1937) and on direct measurements
(West, 1983)

PAO2 PACO2 PAN2 PAH2O BP Altitude

(mmHg) (mmHg) (mmHg) (mmHg) (mmHg) (m)

30 20 189 47 286 ~7500

35 7 164 47 253 ~8850

O2-CO2 Diagram from Rahn and Otis, 1949 with
data from AMREE, OEI, OEII, (West, 1983)
 Model of the respiratory system. O2 flow (MO2) is shown together with differences in O2
partial pressures at the various levels of the O2 cascade. G=conductance
PIO2
Medium Air
Air or O2 Flow = Pressure gradient Conductance

Exchanging organs water

Ventilatory cross c .
(lungs, parabronchia, gills) MO2 = (PI -PE)O2 G vent
convection counter c
ventil./perfusion ratio
pool diffusion, ventilation
Air-water/ .
shunts MO2 = (PA-Pa)O2 G diff
blood barrier
cp
.
Circulatory blood flow (Q)
a Convection v .
Blood (b) Hb concentration MO2 = (PA-Pv)O2 G perf
Hb-O2 affinity
ct
Blood/tissue barrier (t) Capillary .
Diffusion denity MO2 = (Pa-Pt)O2 G diff

Interstitial fluid Diffusion

Cell membrane Diffusion

Myoglobin .
Mitochondrial MO2 = (Pt -Pm)O2 G t
Cell enzymes
O2 CO2
Consumption Production
Energy
.
 .
VO2max as a function of altitude in acute
and chronic hypoxia in caucasian subjects
100

80
VO2max (% asl)

60

40
. Chronic Hypoxia
20 Acute Hypoxia

0
0 1 2 3 4 5 6 7 8 9
Altitude (km)
 .
Determinants of VO2max
Maximum pulmonary ventilation
Lung diffusing capacity
Blood flow (maximum heart rate and cardiac
output)
Hb concentration
HbO2 affinity
Muscle capillarization
Muscle mitochondrial enzymes
Muscle myoglobin
Respiratory quotient
 Maximum pulmonary ventilation
200

5.800 m
VE BTPS (l min-1) 150 (380 Torr)
7.440 m
(300 Torr)

100
0m

.
50

0
0 REST 1 2 3 4
.
VO2 (l min-1)
 -Increase of overall O2 uptake per unit increase of
ventilation in normoxia and in chronic hypoxia.

- O2 cost of ventilation in normoxia and in chronic hypoxia

 Lung diffusing capacity
Normoxia

Hypoxia

Time in capillary (sec) Time in capillary (sec)

Blood flow (maximum heart rate and cardiac output)

.
H.R. (b min-1) Q (l min-1)
220 35
200 30 0m
180 5.050 m
25
160
Caucasians (rest) 20
140 Caucasians (exercise)
Tibetans (rest)
120 Tibetans (exercise) 15
100
10
80
60 5
40 0
-1 0 1 2 3 4 5 6 7 8 Rest Max. exercise
Altitude (km)
 Hb concentration, RBC, Hct
25,0 9 70

22,5 8 65

RBC (10 l )
-1
Hb (g%)

20,0 7 60

Hct (%)
6

17,5 6 55

15,0 5 50

12,5 4 45
0 1000 2000 3000 4000 5000 6000
Altitude (m)
 HbO2 affinity
P50, mmHg

Chronic Altitude
Sea level Acute hypoxia
hypoxia natives

26.3 (C) 28.5 (C) 28.2 (C) 28.8 (A.I.)

Mean values from Mean values from Mean values from Mean values from
literature literature literature literature

26.5 (I) - 28.2 (I) -

Samaja et al., 1979

27.1 (Sh)
Samaja et al., 1979 - - 27.3 (Sh)
Muscle capillarization
Muscle mitochondrial enzymes
%
VARIABLE
change
Muscle mass -10
Fiber O -15
-55
Mitochondrial volume -26
-18

HK =
PFK =
LDH =

MDH -20
HADH -27
CS -23

Cyt Ox -23
HBDH -27
 100 Myoglobin isoforms in
lowlanders and tibetan
highlanders
Kda
2,5
a.u. * *
2
* * * *
1,5 * * *
14
1
pH 3-10 NL
0,5
Nepali Tib. I gen Tib. II gen.
0
LDH PGA NUGM Mb

Myoglobin
Respiratory quotient
2. ANAEROBIC METABOLISM
2.1 Alactic
2.2 Lactacid
 2.1 Alactic
Acute hypoxia
Up to 5000m
.
no effects on wp
Chronic hypoxia
< 5000 m
.
3 weeks: no effect on wp
> 5000 m
.
> 5 weeks : significant decrease of wp
 2.2 Lactacid
15
[LAb]max (mM)

12

6 Operation Everest II
Caucasians
Altitude Natives of different ethnic groups
3 Caucasians (Marconi et Coll., 1994)
Sherpa (personal observation, 1976, 1994)
Caucasians (Marconi et Coll., 1998)
0
0 1 2 3 4 5 6 7 8 9
Altitude (km)